During heavy exercise, an animal's oxygen consumption may exceed that at rest by 10 to 20 fold. Because it is the working skeletal muscle that is setting the demand for oxygen, over 90% of the oxygen that is consumed at the lungs (at Vo2 max) is utilized by the working skeletal muscle. Recently, evidence has been building that one of the most critical steps in the oxygen transport cascade is the transfer of O2 from the hemoglobin in the erythrocytes to the mitochondria within the skeletal muscle. There remain a large number of unresolved questions regarding this process. Among these are: How is delivery coupled to demand; what is their interaction? If there are changes in either capillary transit time (e.g., via increases in mitochondrial capillary), or the aerobic demand of the muscle (e.g., via increases in mitochondrial volume density), how is the balance maintained? What are the adaptive (phenotypically plastic) mechanisms that exist to insure adequate oxygen diffusion (e.g., P50, bohr shift, myoglobin content, heterogeneity of mitochondrial distribution)? The research proposed will explore these questions by exploiting naturally occurring differences in oxygen supply and demand that exist as dependent functions of mammalian body size. Additionally, we propose to couple the allometric model with experimental manipulation of both oxygen delivery (FIO2) and skeletal muscle oxygen delivery/supply to oxygen demands is the critical variable that determines the distribution of mitochondria within the demand is the critical variable that determines the distribution of mitochondria within the muscle fiber (subsarcolemmal vs. intermyofibrillar) as well as the shape of the oxygen dissociation curve (P50). This study is designed to test structure-function hypotheses. This study has an additional educational aim, to train Native American students in all aspects of designing and implementing an experimental study. My goal for the students is that they learn a number of current techniques, including quantitative electron microscopy, physiology and some muscle biochemistry in gaining an understanding of how to perform contemporary hypothesis-driven science. They will be expected to participate in all aspects of this study and its dissemination in presentations to national meetings and publications.